A variety of functional annotations were then intersected with the set of variants using the BEDTools package (19), including the chromatin state segmentation of Ernst et al. (6), and conserved regions by GERP (20) and SiPhy (21,22). To obtain gene annotations, RefSeq genes (23) were downloaded from the UCSC Genome Browser and GENCODE version 7 (24) was downloaded from the project website. BEDTools was then used to calculate the proximity of each variant to a gene by either annotation, as well as the orientation (3′ or 5′) relative to the nearest end of the gene, based on the strand of the gene.
